阿尔茨海默病淀粉样肽神经毒性的离子通道假说
Ion channel hypothesis for Alzheimer amyloid peptide neurotoxicity.
作者信息
Pollard H B, Arispe N, Rojas E
机构信息
Laboratory of Cell Biology and Genetics, NIDDSK, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Cell Mol Neurobiol. 1995 Oct;15(5):513-26. doi: 10.1007/BF02071314.
Abstract
- Alzheimer's disease (AD) is a chronic dementia and neurodegenerative disorder affecting the oldest portions of the population. Brains of AD patients accumulate large amount of the A beta P peptide in amyloid plaques. 2. The A beta P[1-40] peptide is derived by proteolytic processing from a much larger amyloid precursor protein (APP), and has been circumstantially identified as the toxic principle causing cell damage in the disease. 4. The A beta P[1-40] peptide is able to form quite characteristic calcium channels in planar lipid bilayers. These channels have conductances in the nS range, and can dissipate ion gradients quickly. The peptide can also cause equivalent cation conductances in cells. 5. We suggest that amyloid channel blocking agents might be therapeutically useful in Alzheimer's Disease, and have constructed molecular models of the channels to aid in the design of such compounds.
摘要
- 阿尔茨海默病（AD）是一种影响老年人群的慢性痴呆和神经退行性疾病。AD患者的大脑在淀粉样斑块中积累大量β淀粉样蛋白（AβP）肽。2. AβP[1-40]肽是通过蛋白水解加工从一种大得多的淀粉样前体蛋白（APP）衍生而来的，并且已被间接确定为该疾病中导致细胞损伤的毒性成分。4. AβP[1-40]肽能够在平面脂质双分子层中形成相当有特征性的钙通道。这些通道的电导在纳安范围，并且能够迅速消散离子梯度。该肽还能在细胞中引起等效的阳离子电导。5. 我们认为淀粉样通道阻断剂可能在治疗阿尔茨海默病中有用，并构建了通道的分子模型以辅助此类化合物的设计。
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